7-KC modulated the association between AxD and NfL in the corpus callosum splenium (B = 39.39, p = 0.017), genu (B = 68.64, p = 0.000), and fornix (B = 10.97, p = 0.000). Lower Aβ42 levels were associated to lower FA and higher MD, AxD, and RD in the fornix, corpus callosum, inferior longitudinal fasciculus, and hippocampus. The association between AxD and Aβ42 was moderated by 7K-C (p = 0.048). Conclusion This study adds clinical evidence to support the role of 7K-C on axonal integrity and the involvement of cholesterol metabolism in the Aβ42 generation process.Background Cortical complexity plays a central role in the diagnosis and prognosis of age-related diseases. However, little is known about the regional cortical complexity in the context of brain atrophy. Objective We aimed to systematically examine the age-related changes of the cortical complexity of left dorsolateral prefrontal cortex (DLPFC) and its subregions. Methods Two hundred and fourteen cognitively normal adults drawn from the Open Access Series of Imaging Studies (OASIS) were divided into four age groups young, middle-aged, young-old, and old-old. Based on structural magnetic resonance imaging (sMRI) scans, the multiscale measures of cortical complexity included cortical thickness (mm), surface area (mm2), grey matter volume (mm3), density, gyrification index (GI), and fractal dimension (FD). Results Advancing age was associated with reduced grey matter volume, pial surface area, density, and FD of left DLPFC, but correlated with increased cortical thickness and GI. Volumetric measures, cerebrospinal fluid volume in particular, showed better performance to discriminate young-old adults from old-old adults, while FD was more sensitive than the volumetric measures to discriminate young adults and middle-aged adults than the other measures. Conclusion This is the first demonstration that chronological age has a pronounced and differential effect on the cortical complexity of left DLPFC. Our findings suggest that surface-based measures of cortical region, thickness, and gyrification in particular, could be considered as valuable imaging markers for the studies of aging brain and neurodegenerative diseases.Background There are detectable cognitive differences in cognitively unimpaired (CU) individuals with preclinical Alzheimer's disease (AD). Objective To determine whether cross-sectional performance on the Cogstate Brief Battery (CBB) and Auditory Verbal Learning Test (AVLT) could identify 1) CU participants with preclinical AD defined by neuroimaging biomarkers of amyloid and tau, and 2) incident mild cognitive impairment (MCI)/dementia. Method CU participants age 50+ were eligible if they had 1) amyloid (A) and tau (T) imaging within two years of their baseline CBB or 2) at least one follow-up visit. AUROC analyses assessed the ability of measures to differentiate groups. We explored the frequency of cross-sectional subtle objective cognitive impairment (sOBJ) defined as performance ≤-1 SD on CBB Learning/Working Memory Composite (Lrn/WM) or AVLT delayed recall using age-corrected normative data. Results A+T+ (n = 33, mean age 79.5) and A+T- (n = 61, mean age 77.8) participants were older than A-T- participants (n = 146, mean age 66.3), and comparable on sex and education.  https://www.selleckchem.com/TGF-beta.html  Lrn/WM did not differentiate A + T+or A+T- from A-T- participants. AVLT differentiated both A+T+ and A+T- from A-T- participants; 45% of A+T+ and 25% of A+T- participants met sOBJ criteria. The follow-up cohort included 150 CU individuals who converted to MCI/dementia and 450 age, sex, and education matched controls. Lrn/WM and AVLT differentiated between stable and converter CU participants. Conclusion Among CU participants, AVLT helped differentiate A+T+ and A+T- from A-T- participants. The CBB did not differentiate biomarker subgroups, but showed potential for predicting incident MCI/dementia. Results inform future definitions of sOBJ.Background Cortical iron accumulation has been reported as a pathological feature of Alzheimer's disease (AD). The cause of cortical iron elevation in AD is unknown but may be contributed by hemosiderin deposits in cerebral microbleeds that frequently occur in this disease. Objective To investigate the impact of cerebral microbleeds (which are more frequent in AD) on the magnetic susceptibility of the surrounding brain tissue. Methods 32 MRI scans from the Australian Imaging, Biomarker and Lifestyle (AIBL) study were found to have cerebral microbleeds by manual assessment of susceptibility weighted images. Quantitative susceptibility mapping (QSM; an MRI technique that is sensitive to iron) was used to estimate iron content in the tissue surrounding the microbleed in four concentric radii. Furthermore, the mirror regions on the contralateral hemisphere were also demarcated. A simulation analysis was conducted to investigate the effect of QSM imaging on cerebral microbleeds with varying sizes. Results 77 microbleeds were identified from the available scans. The immediate proximal region to the cerebral microbleeds had enhanced tissue susceptibility (∼0.02 PPM), but importantly, this did not extend beyond one voxel radius. This finding with in vivo data was also replicated in a simulation study. However, the presence of microbleeds could lead to over-estimation of tissue QSM in unsupervised quantification, therefore processing methods to avoid this artefact without the need for their manual identification are proposed. Conclusion The local changes in susceptibility due to microbleeds outside the focal lesion are restricted to 1 voxel and may be explained by partial voluming artefacts caused by limited imaging resolution. The susceptibly change induced by the microbleed is a relatively small proportion of tissue and could not account for regional iron changes observed in AD cortex.Background Patients with coronary artery disease have an increased risk for developing vascular cognitive impairment. Endothelial function is often diminished and has been associated with lower cognitive performance in these patients. The link between endothelial function and cognition in coronary artery disease is not fully understood. Angiogenesis may play a role in mediating the association between endothelial function and cognition since angiogenic processes rely heavily on the endothelium. Objective The aim of this study was to determine if markers of angiogenesis mediate the relationship between endothelial function and cognition in coronary artery disease patients. Methods In 50 participants with coronary artery disease, endothelial function was assessed using peripheral arterial tonometry. Vascular endothelial growth factor (pro-angiogenic) and endostatin (anti-angiogenic) were measured in peripheral serum samples. Cognition was assessed using the Montreal Cognitive Assessment. A mediation analysis, using a bias corrected inferential bootstrapping method with 10,000 permutations, was used to determine if vascular endothelial growth factor or endostatin mediated an association between peripheral arterial tonometry measures and cognitive performance on the Montreal Cognitive Assessment.